The objective of this research program is to study the role of the genome of brain cells in the delayed (i.e., minutes to days) responses of the nervous system to the environment. We have chosen steroid hormones for these studies because, as internal messengers secreted in response to changes in the internal and external environment, they have well-described effects on neuroendocrine function and behavior. The aspect of steroid-brain interactions which is the focal point of this application is the dual effect of gonadal steroids (testosterone and estradiol) to reversibly activate sexual behavior and neuroendocrine function in the adult animal and to irreversibly organize the sexual differentiation of the brain in fetal or early neonatal life. In this proposal we consider the similar as well as the different cellular actions of gonadal steroids in these two processes, the development transition between them, and the consequences of sexual differentiation of the brain for the activational effects of the gonadal steroids. We propose to study the lordosis response of the female rat, which is activated by estradiol and progesterone in adult life, with respect to the intrahypothalamic locus of estrogen and progesterone action, the possibly critical role of estrogen induction of progestin receptors in this process, and the timing of steroid action on the genome. An important aspect of gonadal steroid action pertaining to brain sexual differentiation is the conversion of testosterone to estradiol and the action of this estradiol via estrogen receptors. Developmental studies will determine the role of endocrine and neural factors in the ontogeny of estrogen receptors and LHRH, using transplantation of fetal rat hypothalamus to adult brain; the intrahypothalamic locus of estradiol and testosterone action in the neonatal rat responsible for suppressing the lordosis response in the male rat; and the locus of estradiol action and the kinds of proteins formed in oogan cultures of neonatal mouse hypothalamus in which estradiol stimulates neural outgrowth. Studies of RNA and protein synthesis involvement will be undertaken with antibiotic synthesis inhibitors and with labeled precursors, using polyacrylamide gel electrophoresis to separate labeled proteins.